BMP7 induces the differentiation of bone marrow-derived mesenchymal cells into chondrocytes

  • Xiaodan Bai
  • Guangze Li
  • Can Zhao
  • Hongzhang Duan
  • Fujun Qu
Original Article


Injured articular cartilage has a poor capacity for spontaneous healing. So far, a satisfactory solution to repair the injured cartilage has not been found, but transgenic therapy might be a promising treatment. This study aims to evaluate the potential of transfecting bone morphogenetic protein-7 (BMP-7), a secretory protein, into bone marrow-derived mesenchymal stem cells (BMSCs), in inducing the differentiation of bone marrow stromal cells into chondrocytes in vitro. The phenotypes of the cells were observed by alcian blue staining and H&E staining with an inverted microscope. The glycosaminoglycan (GAG) content of BMSCs transfected with pcDNA3.1-BMP7 or induced by inducing medium was examined after 7, 14, or 21 days of incubation. A standard curve as reference for BMSCs’ GAG content was plotted using galacturonic acid. The content of type II collagen in culture medium was detected by ELISA. Our results demonstrated that BMP7-transfected BMSCs or BMSCs incubated with inducing medium possess the ability to differentiate into chondrocytes. BMP7-induced BMSCs secrete type II collagen and GAG. There was no significant difference between BMP7-induced BMSCs in their secreted protein content when compared with the positive control group (TGF-β1 and dexamethasone) (P > 0.05), but there was significant difference in the secreted protein profile when compared with the negative control group (P < 0.05).


Bone morphogenetic protein7 Bone marrow mesenchymal stem cells (BMSCs) Chondrocyte Tissue engineering cartilage 



This work was financially supported by the Natural Science Foundation of Heilongjiang Province, China (Grant No. D2007-70) and the Foundation of Heilongjiang Educational Committee, China (Grant No. 11521170). We thank our colleagues for helpful comments.


  1. 1.
    Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192PubMedCrossRefGoogle Scholar
  2. 2.
    Buckwalter JA (2002) Articular cartilage injuries. Clin Orthop Relat Res 402:21–37PubMedCrossRefGoogle Scholar
  3. 3.
    Buckwalter JA, Mankin HJ (1998) Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 47:487–504PubMedGoogle Scholar
  4. 4.
    Che JH, Zhang ZR, Li GZ, Tan WH, Bai XD, Qu FJ (2010) Application of tissue-engineered cartilage with BMP-7 gene to repair knee joint cartilage injury in rabbits. Knee Surg Sports Traumatol Arthrosc 18:496–503PubMedCrossRefGoogle Scholar
  5. 5.
    Gao J, Caplan AI (2003) Mesenchymal stem cells and tissue engineering for orthopaedic surgery. Chir Organi Mov 88:305–316PubMedGoogle Scholar
  6. 6.
    Ginsberg HS (1996) The ups and downs of adenovirus vectors. Bull N Y Acad Med 73:53–58PubMedGoogle Scholar
  7. 7.
    Hao J, Yao Y, Varshney RR, Wang L, Prakash C, Li H, Wang DA (2008) Gene transfer and living release of transforming growth factor-beta3 for cartilage tissue engineering applications. Tissue Eng Part C Methods 14:273–280PubMedCrossRefGoogle Scholar
  8. 8.
    Hernandez YJ, Wang J, Kearns S, Loiler WG, Poirier A, Flotte TR (1999) Latent adeno-associated virus infection elicits humoral but not cell-mediated immune responses in a nonhuman primate model. J Virol 73:8549–8558PubMedGoogle Scholar
  9. 9.
    Im GI, Kim DY, Shin JH, Hyun CW, Cho WH (2001) Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Joint Surg Br 83:289–294PubMedCrossRefGoogle Scholar
  10. 10.
    Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, Boyde A, Ruspantini I, Chistolini P, Rocca M et al (2000) Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 49:328–337PubMedCrossRefGoogle Scholar
  11. 11.
    Minguell JJ, Erices A, Conget P (2001) Mesenchymal stem cells. Exp Biol Med (Maywood) 226:507–520Google Scholar
  12. 12.
    Nöth U, Rackwitz L, Heymer A, Weber M, Baumann B, teinert A, Schutze N, Jakob F, Eulert J (2007) Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels. J Biomed Mater Res A 83:626–635PubMedGoogle Scholar
  13. 13.
    Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18:959–963PubMedCrossRefGoogle Scholar
  14. 14.
    Piedra PA, Poveda GA, Ramsey B, McCoy K, Hiatt PW (1998) Incidence and prevalence of neutralizing antibodies to the common adenoviruses in children with cystic fibrosis: implication for gene therapy with adenovirus vectors. Pediatrics 101:1013–1019PubMedCrossRefGoogle Scholar
  15. 15.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  16. 16.
    Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74PubMedCrossRefGoogle Scholar
  17. 17.
    Qu FJ, Liu Y, Zhu DL (2008) Construction of tissue-engineered cartilage with BMP7 gene-transfected chondrocytes. J Int Med Res 36:837–847PubMedGoogle Scholar
  18. 18.
    Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386PubMedCrossRefGoogle Scholar
  19. 19.
    Redman SN, Oldfield SF, Archer CW (2005) Current strategies for articular cartilage repair. Eur Cell Mater 9:23–32PubMedGoogle Scholar
  20. 20.
    Toh WS, Liu H, Heng BC, Rufaihah AJ, Ye CP, Cao T (2005) Combined effects of TGFbeta1 and BMP2 in serum-free chondrogenic differentiation of mesenchymal stem cells induced hyaline-like cartilage formation. Growth Factors 23:313–321PubMedCrossRefGoogle Scholar
  21. 21.
    Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76:579–592PubMedGoogle Scholar
  22. 22.
    Yanai T, Ishii T, Chang F, Ochiai N (2005) Repair of large full-thickness articular cartilage defects in the rabbit: the effects of joint distraction and autologous bone-marrow-derived mesenchymal cell transplantation. J Bone Joint Surg Br 87:721–729PubMedCrossRefGoogle Scholar
  23. 23.
    Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM (1994) Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91:4407–4411PubMedCrossRefGoogle Scholar

Copyright information

© International Federation for Medical and Biological Engineering 2011

Authors and Affiliations

  • Xiaodan Bai
    • 1
  • Guangze Li
    • 1
  • Can Zhao
    • 1
  • Hongzhang Duan
    • 1
  • Fujun Qu
    • 1
  1. 1.Department of PharmacyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina

Personalised recommendations